Pelvic organ prolapse in fibulin-5 knockout mice: Pregnancy-induced changes in elastic fiber homeostasis in mouse vagina

Peter G. Drewes, Hiromi Yanagisawa, Barry Starcher, Ian Hornstra, Katalin Csiszar, Spyridon I. Marinis, Patrick Keller, R. Ann Word

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Pelvic organ prolapse is strongly associated with a history of vaginal delivery. The mechanisms by which pregnancy and parturition lead to failure of pelvic organ support, however, are not known. Recently, it was reported that mice widi null mutations in lysyl oxidase-like 1 (LOXL1) develop pelvic organ prolapse. Elastin is a substrate for lysyl oxidase (LOX) and LOXL1, and LOXL1 interacts widi fibulin-5 (FBLN5). Therefore, to clarify the potential role of elastic fiber assembly in the pathogenesis of pelvic organ prolapse, pelvic organ support was characterized in Fbln5-/- mice, and changes in elastic fiber homeostasis in the mouse vagina during pregnancy and parturition were determined. Pelvic organ prolapse in Fbln5-/- mice was remarkably similar to that in primates. The temporal relationship between LOX mRNA and protein, processing of LOXL1 protein, FBLN5 and tropoelastin protein, and desmosine content in the vagina suggest that a burst of elastic fiber assembly and cross linking occurs in the vaginal wall postpartum. Together with the phenotype of Fbln5-/- mice, the results suggest that synthesis and assembly of elastic fibers are crucial for recovery of pelvic organ support after vaginal delivery and that disordered elastic fiber homeostasis is a primary event in the pathogenesis of pelvic organ prolapse in mice.

Original languageEnglish (US)
Pages (from-to)578-589
Number of pages12
JournalAmerican Journal of Pathology
Volume170
Issue number2
DOIs
StatePublished - Feb 2007

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Protein-Lysine 6-Oxidase
Pelvic Organ Prolapse
Elastic Tissue
Vagina
Knockout Mice
Homeostasis
Pregnancy
Desmosine
Tropoelastin
Parturition
Proteins
Elastin
Postpartum Period
Primates
fibulin
Phenotype
Messenger RNA
Mutation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Pelvic organ prolapse in fibulin-5 knockout mice : Pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. / Drewes, Peter G.; Yanagisawa, Hiromi; Starcher, Barry; Hornstra, Ian; Csiszar, Katalin; Marinis, Spyridon I.; Keller, Patrick; Word, R. Ann.

In: American Journal of Pathology, Vol. 170, No. 2, 02.2007, p. 578-589.

Research output: Contribution to journalArticle

Drewes, Peter G. ; Yanagisawa, Hiromi ; Starcher, Barry ; Hornstra, Ian ; Csiszar, Katalin ; Marinis, Spyridon I. ; Keller, Patrick ; Word, R. Ann. / Pelvic organ prolapse in fibulin-5 knockout mice : Pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. In: American Journal of Pathology. 2007 ; Vol. 170, No. 2. pp. 578-589.
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